The Section has continued its studies aimed at elucidating the molecular mechanisms of heritable disorders of connective tissue, specifically osteogenesis imperfecta (OI) and Ehlers-Danlos (EDS), and at applying this information to the treatment of these disorders. One continuing interest of the Section is to identify the collagen mutations in patients with OI and EDS and determine the relationship between the type and location of the mutation and the severity of the connective tissue disorder. Mutations in the a2(I) collagen chain identified by this Section and other labs have provided additional support for the regional model we have proposed. There are three primary projects in the Section. One primary project is to develop selective antisense suppression of the mutant collagen allele as an approach for therapeutic intervention. We have been using hammerhead ribozymes as our selective agent. We have transferred our in vitro success with ribozymes into stable transfected cultured fibroblasts with known collagen mutations. We are currently initiating the generation of transgenic mice expressing hammerhead ribozymes.